#2512 Behaviour of Human Proenkephalin A 119-159 (penKid) in an in vitro model of hemoadsorption

Abstract

Abstract Background and Aims Proenkephalin A 119-159 (penKid) is a stable surrogate marker for enkephalins (endogenous opioids regulating kidney function). Different clinical studies have shown severity-dependent increased penKid levels in patients with sepsis-associated acute kidney injury (AKI), indicating that penKid can be used for prediction and diagnosis of AKI and need of renal replacement therapy (RRT) and even subclinical forms of AKI. In the absence of targeted therapies, organ support in terms of RRT is the ultimate treatment in severe AKI cases. Hemoadsorption is utilized as an adjunctive therapy in septic patients. The aim of this study is to define the penKid removal ratio in conditions of in vitro hemoadsorption (HA) using a synthetic microporous hemo-compatible resin. Method The lyophilized peptide was solved in 20 mM Dipotassium phosphate, 6 mM Disodium EDTA [pH 8], avoiding concentrations higher than 1 mg/mL. The compound was diluted in 50 mL of plasma to ensure homogeneous distribution. A batch of blood of 1000 mL with adjusted hematocrit at 30% and albumin concentration of 3 g% was utilized. Blood was spiked with lyophilized synthetic penKid to achieve the target concentration of 600 pmol/L. Blood was adjusted for a volume of 1000 mL, maintained at 37° and continuously stirred during the experiment. HA was performed with QB = 150 mL/min in a closed-loop configuration. A sorbent minimodule of HA380 (Jafron, Zhuhai, People Republic of China) was utilized. Samples were taken at 5, 15, 30, 60 and 120 minutes from the initiation of the circulation. Total removal and reduction ratios were calculated to assess the adsorption. This procedure was repeated three times. Results Initial penKid concentrations in blood corresponded to the desired target. In the three experiments penKid concentrations displayed a consistent decrease that approached 75% removal ratio at 120 minutes (Figs 1 and 2). Minimal variability was observed confirming a consistent behavior of the interaction between the sorbent and the molecule. Conclusion The results suggest that penKid is effectively removed during hemoadsorption and its levels should be evaluated in light of these results when in vivo hemoadsorption is carried out in critically ill patients.